Liver researcher: Defeating cancer may be about curbing not curing

When researcher
Wendong Huang
, Ph.D., sizes up his opponent — liver cancer — he sees a wily foe that resists being vanquished.

Wendong Huang strives for new insights into metabolism and liver cancer. What he discovers could help tame the disease. (Photo credit: Walter Urie)

“Some diseases are very distinct. Maybe it’s one virus that causes a disease or one gene mutation,” said the associate professor in City of Hope’s Division of Gene Regulation and Drug Discovery. “Cancer is more complicated. You cannot treat it just as one factor that caused this cancer. It’s always a combination.”

His assessment isn’t an excuse for pessimism. Instead, it’s an argument for an alternate way of approaching the disease — forcing it into submission without eliminating it altogether.

Huang studies a nuclear hormone receptor called FXR and a membrane receptor called TGR5. These proteins are activated by bile acids to turn genes on and off, playing a key role in regulating metabolism. Just as they influence metabolism bodywide, they also seem to affect the metabolism of cancer cells. His investigations suggest that activating these receptors could play a role in controlling liver cancer.

Huang targets factors that affect tumor metabolism because one key trademark of cancer is out-of-control growth, which carries with it significant energy demands.

“If we can control this — if the cancer cannot divide — we can achieve a fine result for patients even if the cancer cell is still there. I don’t think we need to kill every last cancer cell,” said Huang.

Most of the standard treatments of today are designed to kill cancer — by cutting it away or attacking it with harsh chemicals or radiation. The trade-off is collateral damage to healthy cells. This damage results in the familiar, sometimes long-lasting, side effects of cancer treatment.

By contrast, Huang points to Gleevec, a drug for chronic myelogenous leukemia (CML) and other cancers. When it first gained Food and Drug Administration approval in 2001, it was lauded as a “magic bullet.”

A targeted therapy, Gleevec wrestles CML under control, enabling patients to return to health, without destroying every last cancerous cell. Some describe Gleevec as turning a life-threatening disease into something more like a chronic condition.

“I think that this is a very good example for cancer treatment. If we know the most important factors that really cause this kind of cancer, we can use targeted therapy to control it.”

Huang hopes his work leads to the next breakthrough targeted drug like Gleevec. But the road may be a long one. That drug’s success hinges on targeting the single abnormal protein that spurs CML; most cancers involve the action of a multitude of genes.